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      Targeting Epidermal Growth Factor Receptor (EGFR) in Pediatric Colorectal Cancer

      case-report

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          Abstract

          Background: Colorectal carcinoma (CRC) is very rare in the pediatric and adolescent age range and clinical management is performed according to adult protocols. We report, for the first time in the literature, a case of a child with metastatic CRC successfully treated with panitumumab associated to chemotherapy. Methods: A twelve-year-old male was diagnosed with CRC with nodal metastasis and peritoneal neoplastic effusion. After performing a genetic evaluation, in light of the absence of mutations in RAS family genes, anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody, panitumumab, was added to chemotherapy FOLFOXIRI. Results: The child successfully responded to therapy with normalization of the Carbohydrate Antigen (CA) 19.9 value after the third cycle of treatment. After the sixth cycle, he underwent surgery that consisted in sigmoid resection with complete D3 lymphadenectomy. At histological evaluation, no residual neoplastic cells were detectable in the surgical specimen. He completed 12 cycles of chemotherapy plus panitumomab and he is alive without disease 14 months from diagnosis. Conclusions: Our results suggest performing mutational screening for colorectal cancer also in the pediatric setting, in order to orient treatment that should include targeted therapies.

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          Most cited references32

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          Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.

          To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC). Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS). A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials. The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.
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            Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.

            Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.
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              The distinctive biology of cancer in adolescents and young adults.

              One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                11 February 2020
                February 2020
                : 12
                : 2
                : 414
                Affiliations
                [1 ]Department of Pediatric Onco-Hematology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy; mdebora.depasquale@ 123456opbg.net (M.D.D.P.); raffaele.cozza@ 123456opbg.net (R.C.)
                [2 ]Surgical Oncology Unit, Department of Surgery, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy; alessandro.crocoli@ 123456opbg.net (A.C.); alessandro.inserra@ 123456opbg.net (A.I.)
                [3 ]Digestive Endoscopy and Surgery Unit, Department of Surgery, Bambino Gesù Children’s Hospital-IRCCS, 00165 Rome, Italy; tamara.caldaro@ 123456opbg.net
                [4 ]Department of Laboratories, Genetic Unit, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy; martina.rinelli@ 123456opbg.net
                [5 ]Oncology Unit, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Via Giustiniano, 04011 Aprilia, Italy; gianpaolo.spinelli@ 123456uniroma1.it
                [6 ]Department of Laboratories, Pathology Unit, IRCCS Bambino Gesù Children’s Hospital, 00165 Rome, Italy; paola.francalanci@ 123456opbg.net
                Author notes
                Author information
                https://orcid.org/0000-0001-7691-3314
                https://orcid.org/0000-0001-9047-2383
                https://orcid.org/0000-0002-8502-3310
                https://orcid.org/0000-0002-5663-8674
                https://orcid.org/0000-0002-4747-1032
                Article
                cancers-12-00414
                10.3390/cancers12020414
                7072611
                32053874
                04c50cec-eaca-4285-800e-2b283631e57e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 December 2019
                : 04 February 2020
                Categories
                Case Report

                anti-egfr,panitumumab,childhood,colorectal cancer
                anti-egfr, panitumumab, childhood, colorectal cancer

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